tbuckley/cabot-search huggingface dataset:
Corrigendum to “Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial” [J Infect 84(6) (2022) 795–813, 5511]
Authors: Xinxue Liu, Alasdair Ps Munro, Shuo Feng, Leila Janani, Parvinder K Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Wanwisa Dejnirattisai, Kate Dodd, Yvanne Enever, Ehsaan Qureshi, Anna L Goodman, Christopher A Green, Linda Harndahl, John Haughney, Alexander Hicks, Agatha A van der Klaauw, Jonathan Kwok, Vincenzo Libri, Martin J Llewelyn, Alastair C McGregor, Angela M Minassian, Patrick Moore, Mehmood Mughal, Yama F Mujadidi, Kyra Holliday, Orod Osanlou, Rostam Osanlou, Daniel R Owens, Mihaela Pacurar, Adrian Palfreeman, Daniel Pan, Tommy Rampling, Karen Regan, Stephen Saich, Teona Serafimova, Dinesh Saralaya, Gavin R Screaton, Sunil Sharma, Ray Sheridan, Ann Sturdy, Piyada Supasa, Emma C Thomson, Shirley Todd, Chris Twelves, Robert C Read, Sue Charlton, Bassam Hallis, Mary Ramsay, Nick Andrews, Teresa Lambe, Jonathan S Nguyen-Van-Tam, Victoria Cornelius, Matthew D Snape, Saul N Faust
Journal: Journal of Infection (2023)
Development of a Patient-Reported Outcome Measure to Assess Symptoms Associated with Cataract Surgery and Intraocular Lens Implants
Authors: Ron D. Hays, Scott MacRae, Jack Holladay, Michelle E. Tarver, Flora Lum, Walter Stark, Beverly Weidmer, Nisha Kumar, George Lau, Tieuvi Nguyen, Steven Schallhorn, Malvina Eydelman, Samuel Masket
Journal: Ophthalmology (2023)
Explainable artificial intelligence incorporated with domain knowledge diagnosing early gastric neoplasms under white light endoscopy
Authors: Zehua Dong, Junxiao Wang, Yanxia Li, Yunchao Deng, Wei Zhou, Xiaoquan Zeng, Dexin Gong, Jun Liu, Jie Pan, Renduo Shang, Youming Xu, Ming Xu, Lihui Zhang, Mengjiao Zhang, Xiao Tao, Yijie Zhu, Hongliu Du, Zihua Lu, Liwen Yao, Lianlian Wu, Honggang Yu
Journal: npj Digital Medicine (2023)

White light endoscopy is the most pivotal tool for detecting early gastric neoplasms. Previous artificial intelligence (AI) systems were primarily unexplainable, affecting their clinical credibility and acceptability. We aimed to develop an explainable AI named ENDOANGEL-ED (explainable diagnosis) to solve this problem. A total of 4482 images and 296 videos with focal lesions from 3279 patients from eight hospitals were used for training, validating, and testing ENDOANGEL-ED. A traditional sole deep learning (DL) model was trained using the same dataset. The performance of ENDOANGEL-ED and sole DL was evaluated on six levels: internal and external images, internal and external videos, consecutive videos, and man-machine comparison with 77 endoscopists in videos. Furthermore, a multi-reader, multi-case study was conducted to evaluate the ENDOANGEL-ED's effectiveness. A scale was used to compare the overall acceptance of endoscopists to traditional and explainable AI systems. The ENDOANGEL-ED showed high performance in the image and video tests. In man-machine comparison, the accuracy of ENDOANGEL-ED was significantly higher than that of all endoscopists in internal (81.10% vs. 70.61%, p < 0.001) and external videos (88.24% vs. 78.49%, p < 0.001). With ENDOANGEL-ED's assistance, the accuracy of endoscopists significantly improved (70.61% vs. 79.63%, p < 0.001). Compared with the traditional AI, the explainable AI increased the endoscopists' trust and acceptance (4.42 vs. 3.74, p < 0.001; 4.52 vs. 4.00, p < 0.001). In conclusion, we developed a real-time explainable AI that showed high performance, higher clinical credibility, and acceptance than traditional DL models and greatly improved the diagnostic ability of endoscopists.
Timing and sequence of vaccination against COVID-19 and influenza (TACTIC): a single-blind, placebo-controlled randomized clinical trial
Authors: Elisabeth A. Dulfer, Büsra Geckin, Esther J.M. Taks, Corine H. GeurtsvanKessel, Helga Dijkstra, Liesbeth van Emst, Christa E. van der Gaast – de Jongh, Djenolan van Mourik, Petra C. Koopmans, Jorge Domínguez-Andrés, Reinout van Crevel, Josephine S. van de Maat, Marien I. de Jonge, Mihai G. Netea
Journal: The Lancet Regional Health - Europe (2023)

Novel mRNA-based vaccines have been used to protect against SARS-CoV-2, especially in vulnerable populations who also receive an annual influenza vaccination. The TACTIC study investigated potential immune interference between the mRNA COVID-19 booster vaccine and the quadrivalent influenza vaccine, and determined if concurrent administration would have effects on safety or immunogenicity.TACTIC was a single-blind, placebo-controlled randomized clinical trial conducted at the Radboud University Medical Centre, the Netherlands. Individuals ≥60 years, fully vaccinated against COVID-19 were eligible for participation and randomized into one of four study groups: 1) 0.5 ml influenza vaccination Vaxigrip Tetra followed by 0.3 ml BNT162b2 COVID-19 booster vaccination 21 days later, (2) COVID-19 booster vaccination followed by influenza vaccination, (3) influenza vaccination concurrent with the COVID-19 booster vaccination, and (4) COVID-19 booster vaccination only (reference group). Primary outcome was the geometric mean concentration (GMC) of IgG against the spike (S)-protein of the SARS-CoV-2 virus, 21 days after booster vaccination. We performed a non-inferiority analysis of concurrent administration compared to booster vaccines alone with a predefined non-inferiority margin of -0.3 on the log10-scale.154 individuals participated from October, 4, 2021, until November, 5, 2021. Anti-S IgG GMCs for the co-administration and reference group were 1684 BAU/ml and 2435 BAU/ml, respectively. Concurrent vaccination did not meet the criteria for non-inferiority (estimate -0.1791, 95% CI -0.3680 to -0.009831) and antibodies showed significantly lower neutralization capacity compared to the reference group. Reported side-effects were mild and did not differ between study groups.Concurrent administration of both vaccines is safe, but the quantitative and functional antibody responses were marginally lower compared to booster vaccination alone. Lower protection against COVID-19 with concurrent administration of COVID-19 and influenza vaccination cannot be excluded, although additional larger studies would be required to confirm this.EudraCT: 2021-002186-17.The study was supported by the ZonMw COVID-19 Programme.
Author Correction: Association of step counts over time with the risk of chronic disease in the All of Us Research Program
Authors: Hiral Master, Jeffrey Annis, Shi Huang, Joshua A. Beckman, Francis Ratsimbazafy, Kayla Marginean, Robert Carroll, Karthik Natarajan, Frank E. Harrell, Dan M. Roden, Paul Harris, Evan L. Brittain
Journal: Nature Medicine (2023)
Diagnosis and management of bipolar disorders
Authors: Fernando S Goes
Journal: BMJ (2023)

Abstract Bipolar disorders (BDs) are recurrent and sometimes chronic disorders of mood that affect around 2% of the world’s population and encompass a spectrum between severe elevated and excitable mood states (mania) to the dysphoria, low energy, and despondency of depressive episodes. The illness commonly starts in young adults and is a leading cause of disability and premature mortality. The clinical manifestations of bipolar disorder can be markedly varied between and within individuals across their lifespan. Early diagnosis is challenging and misdiagnoses are frequent, potentially resulting in missed early intervention and increasing the risk of iatrogenic harm. Over 15 approved treatments exist for the various phases of bipolar disorder, but outcomes are often suboptimal owing to insufficient efficacy, side effects, or lack of availability. Lithium, the first approved treatment for bipolar disorder, continues to be the most effective drug overall, although full remission is only seen in a subset of patients. Newer atypical antipsychotics are increasingly being found to be effective in the treatment of bipolar depression; however, their long term tolerability and safety are uncertain. For many with bipolar disorder, combination therapy and adjunctive psychotherapy might be necessary to treat symptoms across different phases of illness. Several classes of medications exist for treating bipolar disorder but predicting which medication is likely to be most effective or tolerable is not yet possible. As pathophysiological insights into the causes of bipolar disorders are revealed, a new era of targeted treatments aimed at causal mechanisms, be they pharmacological or psychosocial, will hopefully be developed. For the time being, however, clinical judgment, shared decision making, and empirical follow-up remain essential elements of clinical care. This review provides an overview of the clinical features, diagnostic subtypes, and major treatment modalities available to treat people with bipolar disorder, highlighting recent advances and ongoing therapeutic challenges.
A phase 2 study of oral difelikefalin in subjects with chronic kidney disease and moderate-to-severe pruritus
Authors: Gil Yosipovitch, Ahmed Awad, Robert H. Spencer, Catherine Munera, Frédérique Menzaghi
Journal: Journal of the American Academy of Dermatology (2023)

Chronic pruritus is burdensome for patients with chronic kidney disease (CKD).We evaluated difelikefalin efficacy and safety in reducing itch in subjects with non-dialysis-dependent CKD and those undergoing hemodialysis (HD).This phase 2, double-blind, randomized, placebo-controlled, dose-finding study enrolled non-dialysis-dependent CKD (stage 3-5) and HD subjects with moderate-to-severe pruritus. Subjects were equally randomized to oral difelikefalin (0.25, 0.5, or 1.0 mg) or placebo once daily for 12 weeks. The primary end point was the change in the weekly mean Worst Itching Intensity Numeric Rating Scale (WI-NRS) score at week 12.Two hundred sixty-nine subjects were randomized (mean [SD] baseline WI-NRS: 7.1 [1.2]). Difelikefalin 1.0 mg significantly reduced weekly mean WI-NRS scores versus placebo at week 12 (P = .018), with numerical reductions observed with difelikefalin 0.25 and 0.5 mg. At week 12, 38.6% of subjects receiving difelikefalin 1.0 mg achieved a complete response (WI-NRS 0-1) versus 14.4% receiving placebo. Difelikefalin resulted in ∼20% improvement in itch-related quality-of-life measures. The most common treatment-emergent adverse events were dizziness, fall, constipation, diarrhea, gastroesophageal reflux disease, fatigue, hyperkalemia, hypertension, and urinary tract infection.Study duration was 12 weeks.Oral difelikefalin significantly reduced itch intensity in stage 3-5 CKD subjects with moderate-to-severe pruritus, supporting continued development for this condition.
Part 1: Executive Summary
Authors: Mary Fran Hazinski, Jerry P. Nolan, John E. Billi, Bernd W. Böttiger, Leo Bossaert, Allan R. de Caen, Charles D. Deakin, Saul Drajer, Brian Eigel, Robert W. Hickey, Ian Jacobs, Monica E. Kleinman, Walter Kloeck, Rudolph W. Koster, Swee Han Lim, Mary E. Mancini, William H. Montgomery, Peter T. Morley, Laurie J. Morrison, Vinay M. Nadkarni, Robert E. O'Connor, Kazuo Okada, Jeffrey M. Perlman, Michael R. Sayre, Michael Shuster, Jasmeet Soar, Kjetil Sunde, Andrew H. Travers, Jonathan Wyllie, David Zideman
Journal: Circulation (2010)
Phase I/II trial of everolimus (RAD001) and trastuzumab in patients with trastuzumab-resistant, HER2-overexpressing breast cancer.
Authors: P. H. Morrow, G. M. Wulf, D. J. Booser, J. A. Moore, P. R. Flores, I. E. Krop, E. P. Winer, G. N. Hortobagyi, D. Yu, F. J. Esteva
Journal: Journal of Clinical Oncology (2010)

1014 Background: Hyperactivation of the PI3K pathway has been associated with trastuzumab (T) resistance in breast cancer (BC). Everolimus (E) selectively inhibits the mammalian target of rapamycin (mTOR), which is activated downstream of PI3K. Preclinical studies showed that the combination of E and T can overcome T resistance in human BC xenografts. We conducted a multicenter phase I/II trial to determine the safety and efficacy of E plus T in patients (pts) with T-resistant metastatic breast cancer (MBC). Methods: Eligible pts had history of biopsy- proven HER2-overexpressing BC and radiographic evidence of MBC, progressive disease after T-based therapy for MBC, ≤2 prior T-based regimens and one lapatinib-based regimen for MBC, measurable disease by RECIST, and LVEF ≥50%. Primary objectives were: (1) to identify the optimal dose and pharmacokinetics (PK) of E in combination with T in a phase I trial and (2) to determine the efficacy of E plus T in a phase II trial. In the first phase, we planned to evaluate two dose levels (10 mg and 5 mg). No dose-limiting toxicity was observed with E 10 mg, and this became the phase II dose. All pts received T 8 mg/kg initially, followed by 6 mg/kg every 3 weeks (wks), in combination with E 10 mg daily. Results: Forty-seven pts were evaluable for safety and efficacy. Median age, 50 (28-66). Thirty-nine (83%) pts had visceral disease. Eighteen (38%) had ER-/PR- negative MBC. Of 9 pts who had prior lapatinib therapy, 1 had a partial response (PR) and 1 had stable disease (SD) ≥ 24 wks. Everolimus PK parameters were similar to previous experience with single-agent E. Grade 3/4 toxicities included lymphopenia (13%), hyperglycemia (13%), and mucositis (11%). Seven (15%) pts demonstrated a PR and 9 (19%) pts had SD ≥ 24 wks, equaling a clinical benefit rate of 34%. Pts received a median of 6 cycles (range, 1-17). Median TTP was 3.4 months [range, 1-14]. Circulating tumor cells (CTC) were present at baseline in 95% of pts analyzed (n=21); 13 had ≥ 5 CTC. CTC levels did not correlate with response and were not predictive of progression of disease. Conclusions: The combined therapy of T and E is a well tolerated regimen that demonstrates promising clinical activity in a T- resistant population. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Novartis, Roche Genentech, Novartis, Roche
Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis
Authors: Anna S Quaade, Xing Wang, Julie B K Sølberg, Nina H Ulrich, Benjamin D McCauley, Jacob P Thyssen, Christine Becker, Jeanne D Johansen
Journal: British Journal of Dermatology (2023)

Abstract Background Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. Objectives To characterize the plasma inflammatory signature of CHE. Methods Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, and clinical- and self-reported variables, were performed. Results Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper (Th)2- and Th1-, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe but not mild AD displayed systemic inflammation. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. Conclusions Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.
Hardison RC. Promoter competition in globin gene control. <i>Blood.</i> 2022;139(14):2089-2091.
Authors: Yao Wang, Zhiqiang Wu, Weidong Han, Dongyao Wang, Zimin Sun, Xiaoyu Zhu, Xiaohu Zheng, Yonggang Zhou, Yichen Lu, Peidong Yan, Huiru Wang, Huilan Liu, Jing Jin, Huaiping Zhu, Rui Sun, Yi Wang, Binqing Fu, Zhigang Tian, Haiming Wei
Journal: Blood (2023)
Limited transmission of SARS-CoV-2 in schools in Ireland during the 2020–2021 school year
Authors: Ciara Kelly, Philippa White, Elizabeth Kennedy, Dearbhail O’Flynn, Aoife Colgan, Mary Ward, Margaret B O’Sullivan, Claire M Buckley, Breda Cosgrove, Melissa Canny, Katharine Harkin, Fiona McGuire, Catherine Lynch, Aidan Ryan, Sean Denyer, Kevin Kelleher, Abigail Collins
Journal: Eurosurveillance (2023)

BackgroundThe role of schools in SARS-CoV-2 transmission has been a debated topic since the beginning of the COVID-19 pandemic.AimTo examine SARS-CoV-2 transmission in all schools in Ireland during the 2020-21 school year.MethodsIn a national descriptive cross-sectional study, we investigated PCR-confirmed cases of COVID-19 among students (aged < 20 years) and staff (aged ≥ 20 years) who attended school during their infectious period to identify school close contacts. SARS-CoV-2 PCR test results of all school close contacts were pooled to obtain an overall positivity rate and to stratify positivity rate by school setting and role (i.e. student or staff).ResultsIn total, 100,474 individuals were tested as close contacts in 1,771 schools during the 2020-21 school year. An overall close contact positivity rate of 2.4% was observed across all schools (n = 2,373 secondary cases). The highest positivity rate was seen in special schools (3.4%), followed by primary (2.5%) and post-primary schools (1.8%) (p < 0.001). Of the close contacts identified, 90.5% (n = 90,953) were students and 9.5% (n = 9,521) were staff. Overall, students had a significantly higher positivity rate than staff (2.4% vs 1.8%, p < 0.001).ConclusionThis study demonstrated that a low level of SARS-CoV-2 transmission occurred in Irish schools during the 2020-21 academic year. In the event of future pandemics, and as the COVID-19 pandemic continues, there is a need to carefully weigh up the harms and benefits associated with disrupted education to mitigate infectious disease transmission before reflexively closing classes or schools.
Maternal Proton Pump Inhibitor Use During Pregnancy and Risk of Low Birth Weight in Offspring in Korea, 2008-2019
Authors: Ahhyung Choi, Yunha Noh, Dong Keon Yon, Ju-Young Shin
Journal: JAMA Network Open (2023)

This cohort study examines whether the risk of low birth weight is associated with prenatal exposure to proton pump inhibitors.
Association of Organizational Pathways With the Delay of Emergency Surgery
Authors: Delphine Lepercq, Tobias Gauss, Anne Godier, Julie Bellet, Guillaume Bouhours, Pierre Bouzat, Emeline Cailliau, Fabrice Cook, Jean-Stéphane David, Fatou Drame, Marvin Gauthier, Antoine Lamblin, Julien Pottecher, Benoit Tavernier, Delphine Garrigue-Huet
Journal: JAMA Network Open (2023)

Importance Delayed admission of patients with surgical emergencies to the operating room occurs frequently and is associated with poor outcomes. In France, where 3 distinct organizational pathways in hospitals exist (a dedicated emergency operating room and team [DET], a dedicated operating room in a central operating theater [DOR], and no dedicated structure or team [NOR]), neither the incidence nor the influence of delayed urgent surgery is known, and no guidelines are available to date. Objective To examine the overall frequency of delayed admission of patients with surgical emergencies to the operating room across the 3 organizational pathways in hospitals in France. Design, Setting, and Participants This prospective multicenter cohort study was conducted in 10 French tertiary hospitals. All consecutive adult patients admitted for emergency surgery from October 5 to 16, 2020, were included and prospectively monitored. Patients requiring pediatric surgery, obstetrics, interventional radiology, or endoscopic procedures were excluded. Exposures Emergency surgery. Main Outcomes and Measures The main outcome was the global incidence of delayed emergency surgery across 3 predefined organizational pathways: DET, DOR, and NOR. The ratio between the actual time to surgery (observed duration between surgical indication and incision) and the ideal time to surgery (predefined optimal duration between surgical indication and incision according to the Non-Elective Surgery Triage classification) was calculated for each patient. Surgery was considered delayed when this ratio was greater than 1. Results A total of 1149 patients were included (mean [SD] age, 55 [21] years; 685 [59.9%] males): 649 in the DET group, 320 in the DOR group, and 171 in the NOR group (missing data: n = 5). The global frequency of surgical delay was 32.5% (95% CI, 29.8%-35.3%) and varied across the 3 organizational pathways: DET, 28.4% (95% CI, 24.8%-31.9%); DOR, 32.2% (95% CI, 27.0%-37.4%); and NOR, 49.1% (95% CI, 41.6%-56.7%) ( P &amp;amp;lt; .001). The adjusted odds ratio for delay was 1.80 (95% CI, 1.17-2.78) when comparing NOR with DET. Conclusions and Relevance In this cohort study, the frequency of delayed emergency surgery in France was 32.5%. Reduced delays were found in organizational pathways that included dedicated theaters and teams. These preliminary results may pave the way for comprehensive large-scale studies, from which results may potentially inform new guidelines for quicker and safer access to emergency surgery.
Modulation of neurotrophic factors in the treatment of dementia, stroke and TBI: Effects of Cerebrolysin
Authors: Konrad Rejdak, Halina Sienkiewicz‐Jarosz, Przemyslaw Bienkowski, Anton Alvarez
Journal: Medicinal Research Reviews (2023)

Abstract Neurotrophic factors (NTFs) are involved in the pathophysiology of neurological disorders such as dementia, stroke and traumatic brain injury (TBI), and constitute molecular targets of high interest for the therapy of these pathologies. In this review we provide an overview of current knowledge of the definition, discovery and mode of action of five NTFs, nerve growth factor, insulin‐like growth factor 1, brain derived NTF, vascular endothelial growth factor and tumor necrosis factor alpha; as well as on their contribution to brain pathology and potential therapeutic use in dementia, stroke and TBI. Within the concept of NTFs in the treatment of these pathologies, we also review the neuropeptide preparation Cerebrolysin, which has been shown to resemble the activities of NTFs and to modulate the expression level of endogenous NTFs. Cerebrolysin has demonstrated beneficial treatment capabilities in vitro and in clinical studies, which are discussed within the context of the biochemistry of NTFs. The review focuses on the interactions of different NTFs, rather than addressing a single NTF, by outlining their signaling network and by reviewing their effect on clinical outcome in prevalent brain pathologies. The effects of the interactions of these NTFs and Cerebrolysin on neuroplasticity, neurogenesis, angiogenesis and inflammation, and their relevance for the treatment of dementia, stroke and TBI are summarized.
Biological rhythms in COVID-19 vaccine effectiveness in an observational cohort study of 1.5 million patients
Authors: Guy Hazan, Or A. Duek, Hillel Alapi, Huram Mok, Alex Ganninger, Elaine Ostendorf, Carrie Gierasch, Gabriel Chodick, David Greenberg, Jeffrey A. Haspel
Journal: Journal of Clinical Investigation (2023)

BACKGROUND. Circadian rhythms are evident in basic immune processes, but it is unclear if rhythms exist in clinical endpoints like vaccine protection. Here, we examined associations between COVID-19 vaccination timing and effectiveness.